A de novo balanced translocation [t(3;11)(p21;q22)] disrupting the TRPC6 gene was identified in an 8-year-old male proband presenting with non-syndromic autism; further functional studies using patient-specific iPSC-derived neuronal cells and mouse models demonstrated that TRPC6 reduction or haploinsufficiency resulted in altered neuronal development, morphology, and function (Griesi-Oliveira et al., 2014).
Molecular Function
The protein encoded by this gene forms a receptor-activated calcium channel in the cell membrane. The channel is activated by diacylglycerol and is thought to be under the control of a phosphatidylinositol second messenger system. Defects in this gene are a cause of focal segmental glomerulosclerosis 2 (FSGS2) [MIM:603965].
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Modeling non-syndromic autism and the impact of TRPC6 disruption in human neurons.
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Adult female C57BL/6 mice were stereotaxically injected with the sh-RNA against the Trpc6 gene product into the hilus of the hippocampus. This was meant to cause gene silencing in the new born neurons of the dentate gyrus.
Allele Type: knock-down
Strain of Origin: Genetic Background: C57BL/6J
ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
The targeting vector was designed to replace exon 7 of the mouse Trpc6 gene, using the 129Sv genomic library. Homozygous offspring were obtained from crossing hets.
Allele Type: Targeted(knock-out)
Strain of Origin: Genetic Background: 1:1 129Sv:C57BL/6J
ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
Heterozygous mice were obtained by the germ line transmission of targeted Trpc6 gene from chimeras. Chimeras were obtained by injection of correctly targeted ES cell lines into C57BL/6 blastocysts.
Allele Type: Targeted(knock-out)
Strain of Origin: Genetic Background: 1:1 129Sv:C57BL/6J
ES Cell Line: Mutant ES Cell Line: Model Source:
Description: Trpc6 knock down sh-rna expressing neurons in mice, show defective neuronal migration in the hippocampus, specifically in the layers of the dentate gyrus whereas the control sh-rna expressing granule cells are found mostly in the inner layer, the trpc6 knock down mice are found mostly in the upper granule layer of the dentate gyrus. the neurons are characterized 28 days post infection of the retrovirus containing sh-rna
Exp Paradigm: Number of cell bodies of new born neurons was calculated in the different (3) layers of the dentate gyrus and the molecular layer of the hippocampus
